1. Field of the Invention
The present invention relates, in general, to optical chromatography systems and methods that employ optical fibers, such as photonic crystal fibers, that are configured to confine light in a fluid filled core and thereby facilitate separation of particles or other targets in the fluid based on size or other properties.
2. Description of the Background Art
Free-space optical manipulation techniques in microfluidic systems have recently generated a significant amount of interest. Such techniques range from traditional optical tweezing (see a recent review by Grier [1]), rotational manipulation of components based on form birefringence [2] to a more recent electro-optic approach such as that by Chiou et al. [3]. As an example of a direct device integration, Wang et al. [4] developed an optical force based cell sorting technique whereby radiation pressure was used to direct rare cells into a separate streams following a green florescent protein (GFP) detection event. Classically the advantage of these optical approaches lies in their ability to provide remote operation and handle individual particles directly as opposed to indirect manipulation of the surrounding flow field.
Though very subtle and complex manipulations have been demonstrated (e.g. Curtis et al. [5]), the majority of these implementations tend to be “binary”. This means that they rely on either the ability to trap or not trap a particle based on whether the conditions for trapping stability are met [6-8]. Recently however a number of works have extended these ideas to exploit the dependence of this trapping potential on the particle properties, enabling much more advanced and subtle operations. As an example, Macdonald et al. [9] demonstrated an optical lattice technique where particles of different sizes were sorted into different streams depending on their strength of repulsion to regions of high optical intensity. In a series of papers, Imasaka and coworkers [10-13] provided the initial foundations for optically driven separation techniques, which they termed optical chromatography (see a recent review by Zhao et al. [14]). These works have recently been extended by Hart et al. who have demonstrated refractive index separation of colloids [15] and other bioparticles [16]. They have also recently integrated this into a microfluidic device format for pathogen detection [17], demonstrating very precise separation between very closely related bacteria Bacillus anthracis and Bacillus thuringiensis and millimeter scale separation [18]. The potential advantage of “Optical Chromatography” is that the propulsive velocity has as much as a 5th power dependence on particle radius. Thus while this technique would not be suitable for cases where de-mixing is undesirable, it would enable as much as 3 orders of magnitude more resolute separations than the current state of the art.
The precision with which particles can be transported and separated with these optical techniques makes them particularly useful for biomedical analysis devices. At present, however, these systems are practically limited by the fundamentals of the free-space optics on which they rely. Specifically, the systems rely on an incident optical beam which is focused by an objective lens on the particles to be separated. The resulting light beam-particle interaction length is limited by either the focal depth or the spot size of the objective lens to usually a few hundred microns. Using a more loosely focused lens (larger spot size) increases the interaction length perhaps to around a millimeter. The required power however scales with the square of the beam radius and as such relatively large optical power is required to perform manipulations over even these relatively small length scales (e.g. Hart et al. [15, 16, 18] used a 700 mW laser to achieve mm scale separation).